DNA repair protein RAD50 is a component of the MRN complex (Mre11-RAD50-Nbs1) responsible for DNA double strand break (DSB) repair. DSBs are caused by ionizing radiation, certain chemotherapy drugs, metabolic reactive oxygen species (ROS), replication errors, and programmed enzymatic activity during meiosis or V(D)J recombination. If left unrepaired, DSBs generate extremely problematic chromosomal translocations, aneuploidy, and carcinogenesis. As a DSB sensor, RAD50 detects and signals the presence of DSBs. RAD50 is a co-activator for DSB-induced cell cycle checkpoint signaling, and operates as a repair-effector in two competing repair pathways: homologous recombination (HR) as well as...